Adverse effects of phthalates on ovarian response to IVF

London, 8 July 2013: Phthalates are among a group of industrial chemicals shown in some
studies to have adverse effects on reproductive health and development, particularly in the
male. As such, they have been collectively defined as "endocrine disruptors", and proposed as
one of several possible environmental exposures responsible for a decline in fertility. They are
classified in two groups - high molecular weight phthalates are used in the production of
plastics, while low molecular weight phthalates are frequently used in the manufacture of
cosmetics.(1) Human studies increasingly report associations of phthalates with various adverse
reproductive outcomes, including altered semen quantity and quality.
Their effect, however, has been less well studied in women, and, despite widespread human
exposure to phthalates, little is known about the effects of low-level, daily exposures to
phthalates on ovarian function - and hence on women's reproductive health.

A new study reported at this year's annual meeting of ESHRE by Dr Irene Souter of
Massachusetts General Hospital and Harvard Medical School in Boston, USA, now suggests that
exposure to phthalates - as measured by levels of phthalate metabolites in urine - is associated
with reduced fertility when defined as a response to IVF treatment. " Our data support the
hypothesis that exposure to specific phthalates might lead to adverse female reproductive
outcomes," said Dr Souter.

The study followed the progress of 231 women (in 325 fresh treatment cycles) scheduled for
IVF at the Massachusetts General Hospital between 2004 and 2012; urine samples were taken at
the start of and throughout treatment and analysed for metabolites of four primary phthalates.

The association of levels of urinary metabolites was then explored with three markers of
response to IVF: the number of eggs produced following ovarian stimulation, embryo
development, and implantation failure.

Results first showed that urinary phthalates were detected in almost all the women, reflecting
the widespread level of exposure. Results also showed:

The odds of implantation failure increased with each rising quartile of two of the urinary
phthalate metabolites. For example, for DEHP (used in vinyl plastic products) the odds of
implantation failure in the highest quartile Q4) was twice that of the lowest (Q1).

There was also an escalating decrease of 4.17% (Q2), 6.19% (Q3) and 11.4% (Q4) in the
number of oocytes retrieved with each DEHP phthalate quartile when compared with Q1 (the
lowest reference quartile).

The results thus showed that urinary concentrations of some commonly used phthalates were
"dose-dependently" associated with a lower yield of IVF oocytes, and an increased risk of
implantation failure. However, the results did not detect any association between levels of
urinary phthalates and rates of fertilisation or embryo development.

Commenting, Dr Souter believes the results "support the hypothesis" that phthalates are
widespread in the environment and may well have an adverse effect on female fertility,
particularly when tested in the model of IVF.

"We are all primarily exposed to phthalates through inhalation and ingestion," she explained. "It
is extremely difficult if not impossible to avoid exposure to phthalates, since they are in so many
products." However, she added, exposure can be reduced by the following:

Limit the use of personal care products with fragrances in them (including many of the modern
baby care products and air fresheners).

Limit use of plastic food storage containers and plastic wraps (certainly do not heat food in
them).

Read the labels and avoid children's toys made of plastics (vinyl) that contain phthalates.

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Notes

Phthalates are a family of synthetic chemicals used in a wide variety of consumer products.
Some phthalates (such as DEHP) are used in polyvinyl chloride (PVC, vinyl) plastics to soften
them. PVC is used in the manufacture of building materials, vinyl household and industrial
products, medical tubing, and blood storage bags. Some phthalates (such as DEP) are used in a
wide variety of personal care products, where they are added to maintain scent and colour.

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